Cell culturing is an essential step in manufacturing many biological products, such as, for example, nucleic acids and antibodies. The process may begin with the addition of a small number of cells (the inoculum) to a vessel containing a liquid media comprising the nutrients essential for metabolism and growth of the cells, and a solid support to which the cells can attach, the solid support immersed in the liquid media. Conditions of temperature, pH, and oxygen and carbon dioxide concentrations are controlled to promote cell growth and division until confluence is reached.
The small scale cultivation and growth of single tissues or tissue grafts on three-dimensional matrices has been described. Use of bioreactors for culturing cells to form a tissue or graft has previously been limited to culturing cells on solid or porous supports suspended in a liquid medium in rigid plastic or glass bioreactors.
Traditional bioreactors are typically designed as stationary reusable tanks or containers. Disposable or single-use bioreactors may utilize plastic sterile bags supported by a non-disposable support structure.
There is a need to develop a flexible wall, disposable bioreactor system for use in ex vivo expansion of cells, tissue, or organs taken from a living body, a system that is designed to provide oxygenation, heat, mixing and pH control as demanded by cells, tissues, grafts, or organs. The ex vivo expanded products could then be transplanted into patients in need thereof. Transplanted tissue can replenish cell population to support regeneration of previously damaged or diseased tissue in the patient. One exemplary use is the growth of vascular cells taken from a living body. Ex vivo expanded vascular cells in the form of a vascular graft could be transplanted into patients in need thereof. Transplanted vascular grafts can support regeneration of previously damaged or diseased vascular vessels in the patient.
Although engineered tissues are increasingly being used in disease therapy in many areas of medicine, for many types of engineered tissues, clinical manufacturing production adheres closely to the original benchtop processes that were used during the early discovery of the technology. Limitations in scale up and automated control of engineered tissue production has led to high costs of goods and potential product variability that may impair clinical outcomes. Hence, there is an urgent need for innovative methods for controllable, scale-able, and affordable tissue production.
Most commercially available vascular grafts are produced from synthetic materials such as expanded polytetrafluoroethylene (PTFE). One yet unsolved problem is that all synthetic grafts suffer from high complication rates when used as arteriovenous (AV) dialysis grafts. These complications can include infection, thrombosis, and neo-intimal hyperplasia leading to graft occlusion. The rates of complications for synthetic AV grafts are so high that the average graft requires multiple interventions during its implantation lifetime, just to maintain patency, that is, the state of being open or unblocked. The high costs of maintaining graft patency, as well as the high morbidity associated with graft infection indicate that there is an urgent need for a better AV graft for dialysis.
Thus, there is an on-going clinical need for a disposable bioreactor system that supports culture, minimizes labor, reduces the risk of breaking sterility, and enables the scale-up production of engineered tissues, organs, and grafts.